1-173201013-G-T

Variant names:

• chr1-173201013-G-T
• rs10489267
• NM_003326.5:c.153+6011C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003326.5(TNFSF4):​c.153+6011C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,210 control chromosomes in the GnomAD database, including 993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (993 hom., cov: 33)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 3 publications found

Genes affected

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	NM_003326.5	c.153+6011C>A		intron_variant	Intron 1 of 2	ENST00000281834.4	NP_003317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000281834.4	c.153+6011C>A		intron_variant	Intron 1 of 2	1	NM_003326.5	ENSP00000281834.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15873 AN: 152092 Hom.: 990 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0962

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15893 AN: 152210 Hom.: 993 Cov.: 33 AF XY: 0.105 AC XY: 7833 AN XY: 74430

African (AFR) AF: 0.161 AC: 6697 AN: 41522

American (AMR) AF: 0.140 AC: 2145 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3470

East Asian (EAS) AF: 0.0697 AC: 362 AN: 5190

South Asian (SAS) AF: 0.0509 AC: 246 AN: 4832

European-Finnish (FIN) AF: 0.0596 AC: 631 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5306 AN: 68000

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.0714 Hom.: 261

Bravo AF: 0.112

Asia WGS AF: 0.0700 AC: 244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.24
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10489267; hg19: chr1-173170152;